Alcoholism and affective disorders frequently occur in the same individuals and in members of the same family. This association may represent the co-existence of two common disease entities in a given individual due to chance or because (a) alcoholism results from self-medication of an underlying affective disorder or (b) depression results from toxic effects of alcohol abuse. A number of studies have attempted to unravel this complex interaction but many unanswered questions still remain. Commonly, the depression disappears within two weeks of abstinence, however, it may have a prolonged course similar to primary depressive illness. A causal relationship is inferred from studies which show an increased incidence of alcoholism in families of patients with affective disorders, a high incidence of affective disorder in the families of alcoholics and a high incidence of suicidal behavior associated with both affective disorder and alcoholism. Studies have shown that alcohol may acutely improve the sense of affective well-being but with continued intoxication this improvement may be reversed. During chronic experimental intoxication, alcoholics not only become increasingly depressed but also more anxious. Descriptive studies have shown a large percentage of withdrawing alcoholics experience generalized anxiety and phobic reactions. In this protocol we propose to characterize certain biochemical aspects of depression and anxiety as they occur in alcoholic patients. To do this, we will examine cerebrospinal fluid, plasma for norepinephrine (lying and standing), urine for catecholamine metabolites and employ pharmacological challenge paradigms using lactate, isoproterenol and chlorimipramine.